MacKenzie A, Wilson H L, Kiss-Toth E, Dower S K, North R A, Surprenant A
Institute of Molecular Physiology, University of Sheffield, Sheffield S10 2TN, United Kingdom.
Immunity. 2001 Nov;15(5):825-35. doi: 10.1016/s1074-7613(01)00229-1.
The proinflammatory cytokine interleukin-1beta (IL-1beta) is a secreted protein that lacks a signal peptide and does not follow currently known pathways of secretion. Its efficient release from activated immune cells requires a secondary stimulus such as extracellular ATP acting on P2X(7) receptors. We show that human THP-1 monocytes shed microvesicles from their plasma membrane within 2-5 s of activation of P2X(7) receptors. Two minutes after such stimulation, the released microvesicles contained bioactive IL-1beta, which only later appeared in the vesicle-free supernatant. We conclude that microvesicle shedding is a major secretory pathway for rapid IL-1beta release from activated monocytes and may represent a more general mechanism for secretion of similar leaderless secretory proteins.
促炎细胞因子白细胞介素-1β（IL-1β）是一种分泌蛋白，它缺乏信号肽且不遵循目前已知的分泌途径。其从活化免疫细胞的有效释放需要诸如细胞外ATP作用于P2X(7)受体这样的二次刺激。我们发现，人THP-1单核细胞在P2X(7)受体激活后2至5秒内从其质膜脱落微泡。这种刺激两分钟后，释放的微泡含有生物活性IL-1β，而其随后才出现在无泡的上清液中。我们得出结论，微泡脱落是活化单核细胞快速释放IL-1β的主要分泌途径，并且可能代表了类似无信号肽分泌蛋白分泌的更普遍机制。
